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The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.

Publication ,  Journal Article
Ruthig, VA; Friedersdorf, MB; Garness, JA; Munger, SC; Bunce, C; Keene, JD; Capel, B
Published in: Development
July 25, 2019

The adult spermatogonial stem cell population arises from pluripotent primordial germ cells (PGCs) that enter the fetal testis around embryonic day (E)10.5. PGCs undergo rapid mitotic proliferation, then enter prolonged cell cycle arrest (G1/G0), during which they transition to pro-spermatogonia. In mice homozygous for the Ter mutation in the RNA-binding protein Dnd1 (Dnd1Ter/Ter ), many male germ cells (MGCs) fail to enter G1/G0 and instead form teratomas: tumors containing many embryonic cell types. To investigate the origin of these tumors, we sequenced the MGC transcriptome in Dnd1Ter/Ter mutants at E12.5, E13.5 and E14.5, immediately prior to teratoma formation, and correlated this information with DO-RIP-Seq-identified DND1 direct targets. Consistent with previous results, we found DND1 controls downregulation of many genes associated with pluripotency and active cell cycle, including mTor, Hippo and Bmp/Nodal signaling pathway elements. However, DND1 targets also include genes associated with male differentiation, including a large group of chromatin regulators activated in wild-type but not mutant MGCs during the E13.5 and E14.5 transition. Results suggest multiple DND1 functions and link DND1 to initiation of epigenetic modifications in MGCs.

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Published In

Development

DOI

EISSN

1477-9129

Publication Date

July 25, 2019

Volume

146

Issue

19

Location

England

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Signal Transduction
  • Repressor Proteins
  • RNA-Binding Proteins
  • Pluripotent Stem Cells
  • Neoplasm Proteins
  • Mutation
  • Mice
  • Male
 

Citation

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Ruthig, V. A., Friedersdorf, M. B., Garness, J. A., Munger, S. C., Bunce, C., Keene, J. D., & Capel, B. (2019). The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming. Development, 146(19). https://doi.org/10.1242/dev.175950
Ruthig, Victor A., Matthew B. Friedersdorf, Jason A. Garness, Steve C. Munger, Corey Bunce, Jack D. Keene, and Blanche Capel. “The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.Development 146, no. 19 (July 25, 2019). https://doi.org/10.1242/dev.175950.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

July 25, 2019

Volume

146

Issue

19

Location

England

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Signal Transduction
  • Repressor Proteins
  • RNA-Binding Proteins
  • Pluripotent Stem Cells
  • Neoplasm Proteins
  • Mutation
  • Mice
  • Male